Relating Diesel Exhaust Exposure to Respiratory and Immune Outcomes in Early Life The goal of this career development plan is to help Dr. Paloma Beamer, an environmental engineer, launch an independent biomedical research program. Asthma is a heterogeneous disease and the natural history, risk factors and clinical expression of the disease differ between asthma and wheezing phenotypes. Common to all forms of asthma is intermittent or persistent airway inflammation during critical time periods of development as a result of altered immune responses to viral infection, allergic sensitization, or environmental irritants. Vehicle exhaust is the primary source of air pollution in urban environments, where asthma prevalence rates are highest. Exposure to diesel exhaust has been associated with respiratory outcomes including asthma and decreased lung function in epidemiological studies and has also been linked with airway inflammation via in vivo human laboratory studies. The main objective of the research plan is to assess longitudinally the role of diesel-related pollutant exposure during infancy in developmental alterations of the immune and respiratory systems that lead to transient early life wheezing or asthma. The proposed project will use data collected from two on-going prospective birth cohort studies that provide extensive longitudinal data for 1730 children on IgE, cytokines, lung function and respiratory symptoms. To complete the aims, Dr. Beamer will use GIS techniques to model diesel-related pollution exposure based on birth and childhood addresses. She will then assess if diesel-related pollutant exposure in early life is associated with: (1) increased incidence of asthma-related respiratory symptoms;(2) decreased lung function;(3) increased bronchial responsiveness;(4) predominance of Th2 versus Th1 cytokine production and (5) increased allergic sensitization as measured by total and allergen-specific IgE and skin prick tests. Findings from these analyses will aid Dr. Beamer in designing age- appropriate interventions that she can evaluate in future community-based trials aimed at the primary prevention of asthma. This research plan forms the basis of a 5-year career development plan for Dr. Beamer under the mentorship of Dr. Fernando Martinez (respiratory diseases, epidemiology), Dr. Lynn Gerald (asthma, community-based research), Dr. Duane Sherrill (biostatistics), and Dr. Eric Betterton (atmospheric chemistry and physics). Additional collaborators include Dr. Anne Wright (asthma epidemiology) and Dr. Andrew Comrie (urban air pollution, spatial analysis). This interdisciplinary group has designed a career development program that includes (1) formal training in biostatistics, epidemiology, immunotoxicology, spatial analysis, intervention development and evaluation, (2) regular meetings with mentors and collaborators, (3) participation in seminars, (4) presenting results at scientific meetings, (5) publishing in peer-reviewed journals, and (6) submitting an R01. Completion of this career development plan will establish Dr. Beamer as a researcher at the interface of environmental engineering and epidemiology, and position her to design and evaluate novel interventions aimed at reducing the burden of respiratory disease from environmental exposures.